Intestinal macrophages and their interaction with the enteric nervous system in health and inflammatory bowel disease

Abstract

Over the past decades, there has been an increasing understanding of cellular and molecular mechanisms that mediate modulation of the immune system by the autonomic nervous system. The discovery that vagal nerve stimulation (VNS) attenuates endotoxin-induced experimental sepsis paved the way for further studies investigating neuro-immune interaction. In particular, great attention is now given to intestinal macrophages: several studies report the existence of both intrinsic and extrinsic neural mechanisms by which intestinal immune homoeostasis can be regulated in different layers of the intestine, mainly by affecting macrophage activation through neurotransmitter release. Given the important role of inflammation in numerous disease processes, such as inflammatory bowel disease (IBD), cholinergic anti-inflammatory mechanisms are under intense investigation both from a basic and clinical science perspective in immune-mediated diseases such as IBD. This review discusses recent insights on the cross-talk between enteric neurons and the immune system, especially focusing on macrophages, and provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response as therapeutic alternative to reinstall immune homoeostasis in intestinal chronic inflammation.

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

“…The Mf4 population is primarily located deep in the mucosa and in the densely innervated submucosa and muscularis propria/externa (75) (Figures 2, 6). Thus, the Mf4 population might be specialized in nervous system interactions, as described in mice (195,(230)(231)(232)(233). However, further investigation is needed to better understand the origin and function of these cells in the human intestine.…”

Activation of Nicotinic Acetylcholine α7 Receptor Attenuates Progression of Monocrotaline-Induced Pulmonary Hypertension in Rats by Downregulating the NLRP3 Inflammasome

“…Alpha7 nicotinic acetylcholine receptor (α7nAChR), firstly identified in the autonomous nervous system, is a ligand-gated ion channel exerted as a regulator in cognitive processes through the modulation of specific neurotransmitters (Marrero et al, 2011; Liu and Su, 2012; Lu et al, 2014). More recently, resident macrophages in different tissues proved to highly express α7nAChR, and the activation of this receptor inhibits the production of inflammatory cytokines, thereby attenuating the local inflammatory response (Yu et al, 2013; Foucault-Fruchard et al, 2018; Meroni et al, 2018). Previous studies demonstrated that the α7nAChR activation mediated bowel, neural, and cardiovascular protection (Yu et al, 2013; Foucault-Fruchard et al, 2018; Meroni et al, 2018).…”

“…More recently, resident macrophages in different tissues proved to highly express α7nAChR, and the activation of this receptor inhibits the production of inflammatory cytokines, thereby attenuating the local inflammatory response (Yu et al, 2013; Foucault-Fruchard et al, 2018; Meroni et al, 2018). Previous studies demonstrated that the α7nAChR activation mediated bowel, neural, and cardiovascular protection (Yu et al, 2013; Foucault-Fruchard et al, 2018; Meroni et al, 2018). Consistent with these data, the administration of α7nAChR agonist has been shown to effectively prevent acute lung injury via inflammation suppression (Ge et al, 2017; Pinheiro et al, 2017).…”

Review article: impact of cigarette smoking on intestinal inflammation—direct and indirect mechanisms

“…In inflammatory bowel disease, the dynamics of blood monocyte differentiation into resident intestinal macrophages is likely altered 154 . Animal models of colitis show increased infiltration of monocytes and immature macrophages into the gut mucosa, which during inflammation subsequently differentiate into mature, proinflammatory macrophages and where they produce a large amount of proinflammatory mediators, such as tumour necrosis factor, interleukin‐6 and nitric oxide 155 . A study on myeloid cell populations isolated from either human colonic inflammatory bowel disease biopsy specimens or murine DSS‐ induced colitis tissue samples has identified that the macrophage‐monocyte balance within the colon is also altered during colitis, with pro‐inflammatory blood monocytes increasingly recruited to the lamina propria 156 .…”